RADICAVA- edaravone injection RADICAVA ORS- edaravone kit

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

EDARAVONE (UNII: S798V6YJRP) (EDARAVONE - UNII:S798V6YJRP)

Available from:

Mitsubishi Tanabe Pharma America, Inc.

INN (International Name):

EDARAVONE

Composition:

EDARAVONE 30 mg in 100 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

RADICAVA and RADICAVA ORS are indicated for the treatment of amyotrophic lateral sclerosis (ALS). RADICAVA and RADICAVA ORS are contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients in this product. Hypersensitivity reactions and anaphylactic reactions have occurred [see Warnings and Precautions (5.1 , 5.2 )]. Risk Summary There are no adequate data on the developmental risk associated with the use of RADICAVA or RADICAVA ORS in pregnant women. In animal studies, administration of edaravone to pregnant rats and rabbits resulted in adverse developmental effects (increased mortality, decreased growth, delayed sexual development, and altered behavior) at clinically relevant doses. Most of these effects occurred at doses that were also associated with maternal toxicity (see Animal Data ) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk for major birth defects and miscarriage in patients with ALS is unknown. Data Animal Data In rats, intravenous administration of edaravone (0, 3, 30, or 300 mg/kg/day) throughout the period of organogenesis resulted in reduced fetal weight at all doses. In dams allowed to deliver naturally, offspring weight was reduced at the highest dose tested. Maternal toxicity was also observed at the highest dose tested. There were no adverse effects on reproductive function in the offspring. A no-effect dose for embryofetal developmental toxicity was not identified; the low dose is less than the recommended human dose of 60 mg for RADICAVA on a body surface area (mg/m2 ) basis. In rabbits, intravenous administration of edaravone (0, 3, 20, or 100 mg/kg/day) throughout the period of organogenesis resulted in embryofetal death at the highest dose tested, which was associated with maternal toxicity. The higher no-effect dose for embryofetal developmental toxicity is approximately 6 times the recommended human dose (RHD) for RADICAVA on a body surface area (mg/m2 ) basis. The effects on offspring of edaravone (0, 3, 20, or 200 mg/kg/day), administered by intravenous injection to rats from GD 17 throughout lactation, were assessed in two studies. In the first study, offspring mortality was observed at the high dose and increased activity was observed at the mid and high doses. In the second study, there was an increase in stillbirths, offspring mortality, and delayed physical development (vaginal opening) at the highest dose tested. Reproduction function in offspring was not affected in either study. Maternal toxicity was evident in both studies at all but the lowest dose tested. The no-effect dose for developmental toxicity (3 mg/kg/day) is less than the RHD on a mg/m2 basis. Reproductive and developmental toxicology studies of edaravone using the oral route have not been conducted Risk Summary There are no data on the presence of edaravone in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Edaravone and its metabolites are excreted in the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RADICAVA and RADICAVA ORS and any potential adverse effects on the breastfed infant from RADICAVA and RADICAVA ORS or from the underlying maternal condition. Safety and effectiveness of RADICAVA or RADICAVA ORS in pediatric patients have not been established Of the 184 patients with ALS who received RADICAVA in 3 placebo-controlled clinical trials, a total of 53 patients were 65 years of age and older, including 2 patients 75 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Product summary:

RADICAVA RADICAVA is supplied as a 30 mg/100 mL (0.3 mg/mL) clear, colorless, sterile solution for intravenous infusion in single-dose polypropylene bags, each overwrapped with polyvinyl alcohol (PVA) secondary packaging containing an oxygen absorber and oxygen indicator, which should be pink to reflect appropriate oxygen levels [see Dosage andAdministration (2.2) and How Supplied/Storage and Handling (16.2) ] . These are supplied in cartons as listed below. NDC 70510-2171-1 30 mg/100 mL (0.3 mg/mL) single-dose bag NDC 70510-2171-2 2 bags per carton RADICAVA ORS RADICAVA ORS is supplied in a white to off-white suspension in multi-dose child resistant 60 mL amber glass bottle which is supplied as two configurations: These are supplied in cartons as listed below: Unit of sale NDS number Package configuration RADICAVA ORS Starter Kit NDC 70510-2321-1 Carton of One (1) bottle of 35mL (105 mg/5 mL dose) NDC 70510-2321-2 Carton of two (2) NDC 70510-2321-1 RADICAVA ORS Kit NDC 70510-2322-1 Carton of One (1) bottle of 50 mL (105 mg/5 ml dose) RADICAVA Store RADICAVA at up to 25°C (77°F). Excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from light. Store in overwrapped package to protect from oxygen degradation until time of use. The oxygen indicator will turn blue or purple if the oxygen has exceeded acceptable levels. Once the overwrap package is opened, use within 24 hours. RADICAVA ORS Pharmacy Store RADICAVA ORS refrigerated between 2ºC to 8ºC (36°F to 46°F) and protect from light. Do not freeze. Store upright. Patient Store RADICAVA ORS upright at room temperature between 20°C to 25°C (68°F to 77°F). Protect from light. Discard 15 days after opening bottle or if unopened 30 days from date of shipment indicated on the carton pharmacy label.

Authorization status:

New Drug Application

Summary of Product characteristics

RADICAVA- EDARAVONE INJECTION
RADICAVA ORS- EDARAVONE
MITSUBISHI TANABE PHARMA AMERICA, INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
RADICAVA OR RADICAVA
ORS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
RADICAVA OR RADICAVA
ORS.
RADICAVA® (EDARAVONE) INJECTION, FOR INTRAVENOUS USE
RADICAVA ORS® (EDARAVONE) ORAL SUSPENSION
INITIAL U.S. APPROVAL: 2017
RECENT MAJOR CHANGES
INDICATIONS AND USAGE
RADICAVA and RADICAVA ORS are indicated for the treatment of
amyotrophic lateral sclerosis (ALS). (1)
DOSAGE AND ADMINISTRATION
•
•
•
DOSAGE FORMS AND STRENGTHS
•
•
CONTRAINDICATIONS
Patients with a history of hypersensitivity to edaravone or any of the
inactive ingredients in RADICAVA
and/or RADICAVA ORS (4)
WARNINGS AND PRECAUTIONS
•
•
ADVERSE REACTIONS
Most common adverse reactions (at least 10% of patients treated with
RADICAVA and greater than
placebo) are contusion, gait disturbance, and headache (6.1)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT MITSUBISHI TANABE
PHARMA AMERICA,
INC. AT 1-888-292-0058 OR FDA AT 1-800-FDA-1088 OR
WWW.FDA.GOV/MEDWATCH.
USE IN SPECIFIC POPULATIONS
Pregnancy: Based on animal data, may cause fetal harm. (8.1)
SEE 17 FOR PATIENT COUNSELING INFORMATION.
REVISED: 12/2023
Indications and Usage (1) 05/2022
Dosage and Administration (2.1, 2.3, 2.4) 05/2022
Contraindications (4) 05/2022
Warnings and Precautions (5.1, 5.2) 05/2022
RADICAVA: The recommended dosage is 60 mg administered as an
intravenous infusion over 60
minutes (2.1)
RADICAVA ORS: The recommended dosage is 105 mg (5 mL) taken orally or
via feeding tube in the
morning after overnight fasting. Food should not be consumed for 1
hour after administration except
water (2.1, 2.3)
For RADICAVA and RADICAVA ORS:
•
•
Initial treatment cycle: daily dosing for 14 days followed by a 14-
day drug-free period (2.1)
Subsequent treatment cycles: daily dosing for 10 days out of 14- day
periods, followed by 14-day
drug-free periods (2.1)
I